Development of a Multi-purpose Equipment for the Repeated Syntheses of ¹¹C-Labelled Alkyl Iodides with High Specific Activity

Abstract

Multi-purpose synthesizer / ^^C-labelled radiopharmaceuticals / [^^CJmethyl iodide / [l-^'C]ethyl iodide / [l-'^C]propyl iodide AbstractA new equipment was developed for the automatic and repeated syntheses of' 'C-labelled alkyl iodides with high specific activity. Using the equipment, 2.2-9.4 GBq of [''C]methyl iodide, [l-"C]ethyl iodide and [l-"C]propyl iodide were produced automatically at the specific activity of 25 -141 GBq/nmoI (at EOS) by irradiating pure N2 gas with 18 MeV protons (14.2 MeV on target) at 5-15 nA for 10-20 minutes. The equipment enabled three times repeated productions of different "C-labelled alkyl iodides in 2.5 hours.

[2-11C]Isopropyl-, [1-11C]Ethyl-, and [11C]Methyl-Labeled Phenoxyphenyl Acetamide Derivatives as Positron Emission Tomography Ligands for the Peripheral Benzodiazepine Receptor: Radiosynthesis, Uptake, and in Vivo Binding in Brain

“…Until now, there has been no report about the efficient synthesis of [ 11 C] 10 with a high specific activity and reproducible radiochemical yield. [ 11 C] 10 has only been reported as a low-yield byproduct in the preparation of [ 11 C] 11 using the Grignard reaction. − As shown in Scheme , the Grignard reagent CH 3 MgBr reacted with [ 11 C]CO 2 to yield [1- 11 C]CH 3 COOMgBr, which further reacted with excess CH 3 MgBr to yield [2- 11 C](CH 3 ) 2 C(OMgBr) 2 . This intermediate was then reduced and iodinated to form [ 11 C] 10 mixed with [ 11 C] 11 , which was produced simultaneously with a low ratio.…”

“…Here, we tried to achieve the selective and efficient synthesis of [ 11 C] 10 or [ 11 C] 11 by promoting or controlling the reaction of two molecules of CH 3 MgBr with [ 11 C]CO 2 . Moreover, to guarantee a reproducible radiochemical yield and a high specific activity of [ 11 C] 10 or [ 11 C] 11 , we constructed an automated synthesis system using a loop method in place of the conventional one-pot method . This system included the following sequences: (1) trapping [ 11 C]CO 2 produced by the cyclotron into a coil, (2) transferring [ 11 C]CO 2 into a loop loaded with CH 3 MgBr to perform the Grignard reaction, (3) producing [ 11 C]alkyl iodide by reduction and iodination in a reactor vessel, (4) purifying them by gas chromatography .…”

“…[34][35][36] As shown in Scheme 2, the Grignard reagent CH 3 MgBr reacted with [ 11 C]11, we constructed an automated synthesis system using a loop method in place of the conventional one-pot method. 36 This system included the following sequences: (1) trapping [ 11 radioactivity to the mass measured from the carrier UV peak on HPLC. No significant UV peaks corresponding to 9 and other chemical impurities were observed in the HPLC charts for these products.…”